A central problem in cancer research is determining the structure of membranes in normal and tumor cells. Conventional transmission and scanning electron microscopy investigations in a number of laboratories are contributing to our knowledge of cell surface characteristics, but it is clear that fresh approaches are also needed. The purpose of this research project is to develop and apply a new kind of microscopy, specifically designed to examine chemical differences in cell surfaces and other membranes. This technique, photoelectron microscopy, utilizes differences in photoelectron quantum yields to visualize the biological surfaces. The escape depth of the electrons is extremely short, which permits mapping of membrane surfaces without interference from the cytoplasmic contents of the cell. The mechanism of contrast is entirely different from transmission and scanning electron microscopy, and it is possible to visualize different biochemical features. In previous grant periods, the feasibility of this approach has been experimentally verified, the first photoelectron images ever seen of biological samples have been reported and the photoelectron quantum yields of the major classes of cell surface components have been determined. Recently a new ultrahigh vacuum photoelectron microscope has been constructed and it was shown that this technique can also detect chemical carcinogens such as benzo(a)pyrene. The major goals for this renewal period include completing the main body of the photoelectron microscope, examining the contrast of the recently selected photoelectric labels against the cell surface background (chicken embryo fibroblasts and mouse 3T3 cells). Other goals include determining the relative contrast of aromatic carcinogens with respect to protein and nucleic acids and calculation of the depth of field in photoelectron microscopy.